Since the isolation and structure elucidation of natural .beta.-lactamase inhibitor clavulanic acid, [Antimicrobial Agents and Chemotherapy, 11, 852 (1977)], as metabolized product of streptomyces clavuligerus, a number of exploratory efforts have been made to isolate another antibiotics. On the other hands, several synthetic studies also have been done for the .beta.-lactam compounds which have 4-oxa-1-azabicyclo[3,2,0] heptan-7-one (oxapenam) skeletons [DT2702091 A1, EP 0057664 A2, DT 2725690 A1, British Patent 1585661, J. Chem. Soc. Perkin Trans I, 2222 (1980), J. Antibiotics, 26, 217 (1983), J. Org. Chem. 50, 3457-3462 (1985), J. Antibiotics, 29, 510 (1986), ibid, 29, 516 (1987), Tetrahedron, 2467 (1987), Chem. Pharm. Bull., 39, 2813-2818 (1991)].
However, in most case, attention were paid to their strong antibacterial, antifungal and .beta.-lactamase inhibitory activities.
We paid attention to the cytotoxic activities of G0069A (JP 61-212587) and Tu1718 (DE 3727651 A1), produced by genus Streptomyces and have been trying to develop them as antitumor agents. However, there were lots of difficulties to obtain these compounds in large scale. For example, only 20 mg of G0069A was isolated from 10 L of fermentation broth even after under well controlled fermentation technique and suitable experimental conditions.
G0069A is chemically very unstable. Isolation process required very complex and special technique and should be done in dark at low temperature. In addition to the complexity in isolation of G0069A from fermentation broth, the synthetic approach is also seemed to be extremely difficult multistep process because they have 5 asymmetric centers and dipeptide side chain. Therefore, it is necessary to get compounds which are relatively easy to synthesis, have shorter chain than G0069A, chemically stable and have strong antitumor activity. ##STR2##